Plasmodium vivax is a major cause of clinical malaria outside of Africa and causes substantial morbidity and economic loss in the developing world. P. vivax presents unique opportunities for invasion blocking vaccine approaches because the parasite is highly selective for reticulocytes and depends on the human DARC protein for invasion. This selectivity differentiates P. vivax from P. falciparum, and provides considerable advantages for development of invasion blocking vaccines. P. vivax binds to DARC via the region II in the P. vivax Duffy binding protein (PvDBPII). Antibodies to PvDBPII inhibit parasite invasion, but the main obstacle to vaccine development is generating high titer functional antibodies that will prevent disease. In this project, we will determine if PvDBPII immunogenicity can be enhanced by conjugating to HepB core antigen particles and investigate whether the antibody response can be further focused by orienting the recombinant protein with the predicted DARC interaction site exposed and covering up off-target polymorphic epitopes. PUBLIC HEALTH RELEVANCE: Plasmodium vivax is a major cause of clinical malaria in many parts of Southeast Asia and Latin America and causes substantial morbidity and economic loss in the developing world. The goal of this project is to use rational immunogen design to enhance the efficacy of a P. vivax vaccine by conjugating PvDBPII recombinant protein on virus-like particles (VLP) and orienting the protein so as to maximize antibody reactivity to the predicted DARC interaction site.